Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about MOVAPO and MOVAPO Pre-Filled Syringe (PFS). It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using MOVAPO or MOVAPO PFS against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

For further information on MOVAPO or MOVAPO PFS please refer to “A guide to the use of apomorphine in the treatment of Parkinson’s Disease for patients and carers” which is available from STADA Pharmaceuticals Australia Pty Ltd.

What MOVAPO and MOVAPO PFS are used for

MOVAPO and MOVAPO PFS contain apomorphine which belongs to a group of medicines called dopaminergic compounds.

Apomorphine is used in the treatment of Parkinson’s disease to reduce the number and severity of bouts of freezing and stiffness (or “off” periods).

This medicine works by acting on dopamine receptors. These receptors help control movement by the body.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive. This medicine is available only with a doctor’s prescription.

Before you use MOVAPO or MOVAPO PFS

When you must not use it

Do not use MOVAPO Injection or MOVAPO PFS if you have an allergy to:

• any medicine containing apomorphine or sodium metabisulfite
• any of the ingredients listed at the end of this leaflet
• certain types of pain killers such as morphine or other opioid analgesics.

Some of the symptoms of an allergic reaction may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin.

Do not use this medicine if you have or have had any of the following medical conditions:

• certain forms of dementia e.g. Alzheimer’s Disease
• severe kidney or liver disease
• problems with circulation of blood in the brain (cerebrovascular disease)
• breathing problems (respiratory depression).

Do not give this medicine to a child under the age of 18 years.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you use it

Tell your doctor or pharmacist if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

• a history of severe nausea and vomiting
• heart disease
• kidney disease
• liver disease
• lung disease
• problem gambling
• any addictive behaviour (e.g. sex, shopping or eating)

Before you use MOVAPO PEN, your doctor will obtain an ECG (electrocardiogram) and will ask for a list of all other medicines you take. This ECG will be repeated in the first days of your treatment and at any point if your doctor thinks this is needed. He or she will also ask you about other diseases you may have, in particular concerning your heart. Some of the questions and investigations may be repeated at each medical visit. If you experience symptoms which may come from the heart, e.g. palpitations, fainting, or near-fainting, you should report this to your doctor immediately. Also, if you experience diarrhoea or start a new medication, this should be reported to your doctor.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor will discuss with you the possible risks and benefits involved.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using MOVAPO or MOVAPO PFS.

Taking other medicines

Tell your doctor or pharmacist if you are taking or using any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines, MOVAPO Injection and MOVAPO PFS may interfere with each other. These include:

• tetrabenazine, a medicine used to treat movement disorders
• metoclopramide, a medicine used to treat nausea
• medicines used to treat some psychiatric (mental) conditions (e.g. phenothiazines, haloperidol, flupenthixol)
• papaverine, a medicine which expands blood vessels
• amphetamines

These medicines may be affected by MOVAPO and MOVAPO PFS, or may affect how well they work. You may need different amounts of your medicines, or you may need to use different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How to use MOVAPO and MOVAPO PFS

Follow all directions given to you by your doctor, nurse or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor, nurse or pharmacist for help.

Do not use MOVAPO or MOVAPO PFS if the solution has turned green or if the solution is cloudy or you can see particles in it.

How much to use

Your doctor will decide what dose you will receive. This depends on your initial response to MOVAPO.

How to use it

You will usually be in hospital when you start using MOVAPO. It is recommended that you are given an anti-nausea drug (domperidone) and that you stop all your other anti-Parkinsonian medication before you start using MOVAPO. This medicine is given as an injection under the skin (subcutaneously), usually into your lower abdomen or outer thigh. It is either injected several times a day or continuously as an infusion (i.e. slow injection via a pump).

MOVAPO PFS is a pre-diluted, pre-filled syringe intended for use as a continuous infusion with a suitable pump/syringe driver. There is no need to dilute MOVAPO PFS prior to use.

When using MOVAPO ampoules to prepare a continuous infusion, it is recommended that MOVAPO is first diluted with an equal volume of sodium chloride 0.9% (normal saline). When using MOVAPO ampoules for intermittent injections, it is not necessary to dilute the MOVAPO.

It is advisable to change the site of injection every time you insert the needle to avoid getting lumps under the skin,

The medicine is for individual patient use only.

You and/or your carers will be trained by hospital staff to recognise when and how to give the injections.

If you use too much (overdose)

Immediately notify your doctor or nurse, or if you are not in hospital, telephone the Poisons Information Centre (telephone 13 11 26 in Australia or 0800 POISON or 0800 764 766 in New Zealand) or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have used too much MOVAPO or MOVAPO PFS. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include severe nausea and vomiting, slow or troubled breathing, restlessness, hallucinations or unconsciousness.

While you are using MOVAPO and MOVAPO PFS

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using MOVAPO or MOVAPO PFS.

Tell any other doctors, dentists and pharmacists who are treating you that you are using this medicine.

If you plan to have surgery, tell the surgeon or anaesthetist that you are using this medicine. It may affect other medicines used during surgery.

If you become pregnant while you are using this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not use MOVAPO or MOVAPO PFS to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how MOVAPO or MOVAPO PFS affects you. This medicine may cause drowsiness, sudden onset of sleepiness, dizziness or light- headedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are using MOVAPO or MOVAPO PFS.

MOVAPO and MOVAPO PFS helps most people with Parkinson’s disease, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

• nausea or vomiting particularly when starting this medicine
• lumps under the skin, rashes or ulcers at the site of injection which are sore, troublesome and may be red and itchy
• drowsiness or suddenly falling asleep
• confusion
• dizziness or light-headedness when standing up, fainting
• headache
• unpleasant metallic taste, sore mouth
• runny nose
• watery eyes
• reduced facial hair growth
• spontaneous penile erection
• weight loss
• yawning.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

• increased involuntary movements or increased shakiness during ‘on’ periods
• aggression, agitation
• pale yellow skin, weakness or breathlessness
• bleeding or bruising
• inability to resist the impulse, drive or temptation to perform an action that could be harmful to you or others, which may include:
  - decreased or increased sexual arousal
  - increased need to gamble
  - compulsive eating, shopping or medication use

The above list includes serious side effects that may require medical attention. Serious side effects are rare or uncommon.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin
• hallucinations (seeing, hearing or feeling things that are not there)

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some people.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress:

• increase in some white blood cells
• high prolactin level in blood.

After using MOVAPO or MOVAPO PFS

Storage

Storage for MOVAPO:
Keep MOVAPO 2 mL and 5 mL ampoules in a cool dry place where the temperature stays below 25°C.

Storage for the Pre-Filled Syringe:
Keep MOVAPO PFS in a cool dry place where the temperature stays below 25°C. Keep unused pre-filled syringes in the outer cardboard carton.

Store in original package in order to protect from light and do not put in the freezer.

MOVAPO and MOVAPO PFS are for single use only. Once opened, the contents of the ampoule or pre-filled syringe should be used immediately. Discard any unused solution.

Do not store MOVAPO, MOVAPO PFS or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

MOVAPO:
MOVAPO is supplied as a clear, colourless, sterile solution that comes in 2 mL or 5 mL glass ampoules in packs of 5.

MOVAPO PFS:
MOVAPO PFS is supplied as a clear, colourless, sterile solution that comes in 10 mL pre-filled glass syringe in packs of 5.

Ingredients

MOVAPO contains 20 mg of apomorphine hydrochloride hemihydrate in 2 mL or 50 mg apomorphine hydrochloride hemihydrate in 5 mL.

MOVAPO PFS contains 50 mg apomorphine hydrochloride hemihydrate in 10 mL.

MOVAPO and MOVAPO PFS also contain:

• sodium metabisulfite
• water for injection
• may contain hydrochloric acid and MOVAPO may contain sodium hydroxide to adjust the pH

MOVAPO and MOVAPO PFS do not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Australia

STADA Pharmaceuticals Australia Pty Ltd,
Suite 2.04,
26 Rodborough Road,
Frenchs Forest NSW 2086,
Australia

New Zealand

CARSL Consulting,
Clinical and Regulatory Services,
24 Side Road, Parkhill Farm, RD10,
Hastings
PO Box 766 Hastings
New Zealand

MOVAPO® is a registered trademark of Britannia Pharmaceuticals Limited.

This leaflet was prepared in January 2021.

Australian Register Numbers

MOVAPO ampoules:

20 mg/2 mL AUST R 142086

50 mg/5 mL AUST R 142093

MOVAPO PFS pre-filled syringe:

50 mg/10 mL AUST R 129948

Published by MIMS April 2021

1 Name of Medicine

Apomorphine hydrochloride hemihydrate.

2 Qualitative and Quantitative Composition

Each 10 mL prefilled syringe contains 50 mg apomorphine hydrochloride hemihydrate.
Sodium metabisulfite is included in the formulation as an antioxidant.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection in prefilled syringe.
Movapo Pre-Filled Syringe (PFS) is a clear solution, practically colourless, odourless and practically free from visible particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Movapo PFS is indicated to reduce the number and severity of 'off' phases in patients with Parkinson's disease severely disabled by motor fluctuations refractory to conventional therapy. Initiation of therapy with apomorphine should be undertaken in a specialist unit in a hospital setting. Conventional therapy should be continued during 'on' phases.

4.2 Dose and Method of Administration

The optimal dosage of Movapo PFS has to be determined on an individual patient basis. Hospital admission under appropriate specialist supervision is advised when establishing a patient's therapeutic regime.
It is essential that the patient is established on the antiemetic domperidone for at least 48-72 hours prior to initiation of therapy.
Movapo PFS is a pre-diluted prefilled syringe intended for use as a continuous subcutaneous infusion with suitable pumps/syringe drivers.
There is no need to dilute Movapo PFS prior to use.
Movapo PFS is for single use in one patient only. Contains no antimicrobial agent. For microbial reasons, once opened the contents of the prefilled syringe should be used for infusion immediately. The infusion site should be changed every 12 hours. Any unused solution should be discarded.
Do not use if the solution has turned green. The solution should be inspected visually prior to use. Only clear, colourless and particle free solution should be used.
Movapo PFS must not be used via the intravenous route.

Patient selection.

Pre-treatment.

After provoking an 'off' phase in motor performance.

Determination of the threshold dose.

Initiation of treatment.

Monitoring treatment.

4.3 Contraindications

Movapo PFS is contraindicated in patients with a known hypersensitivity or allergy to apomorphine, morphine or chemically related products.
Movapo PFS should not be administered to patients with pre-existing neuropsychiatric problems or dementias due to either pathological processes, e.g. Alzheimer's disease, or to patients whose 'on' response to L-dopa is marred by severe dyskinesia, hypotonia or psychotoxicity.
Movapo PFS is also contraindicated in patients with inadequate renal or liver function, unstable coronary vascular disease, cerebrovascular disease, respiratory depression or CNS depression.
Movapo PFS is contraindicated for children and adolescents under 18 years of age.
Movapo PFS is contraindicated in patients with a known hypersensitivity to sodium metabisulfite.
Concomitant use with 5HT₃ antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) is contraindicated (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

For subcutaneous use only (see Section 4.8 Adverse Effects (Undesirable Effects)).
Patients sensitive to morphine or its derivatives may be sensitive to Movapo PFS. Movapo PFS should therefore not be administered to patients with a known hypersensitivity or allergy to apomorphine, morphine or chemically related compounds (see Section 4.3 Contraindications).
Movapo PFS contains sodium metabisulfite which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people (see Section 4.3 Contraindications).
In patients with cardiac decompensation or cerebrovascular disease, vomiting may cause an increase in blood pressure that may lead to haemorrhage and vascular accidents. Apomorphine is therefore contraindicated in these patients (see Section 4.3 Contraindications).
Caution should be used in administering Movapo PFS to patients with a predisposition to nausea and vomiting. Apomorphine may cause an increased risk of persistent vomiting. A risk-benefit assessment should be considered in these patients.
Since apomorphine may produce hypotension, even when given with domperidone pre-treatment, care should be exercised in patients with pre-existing cardiac disease or in patients taking vasoactive medicinal products such as anti-hypertensives, and especially in patients with pre-existing postural hypotension.
Since apomorphine, especially at high doses, may have the potential for QT prolongation, caution should be exercised when treating patients at risk for torsades de pointes arrhythmia.
When used in combination with domperidone, risk factors in the individual patient should be carefully assessed. This should be done before treatment initiation, and during treatment. Important risk factors include serious underlying heart conditions such as congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance. Also medication possibly affecting electrolyte balance, CYP3A4 metabolism or QT interval should be assessed.
Monitoring for an effect on the QTc interval is advisable. An ECG should be performed:
prior to treatment with domperidone;
during the treatment initiation phase;
as clinically indicated thereafter.
The patient should be instructed to report possible cardiac symptoms including palpitations, syncope, or near-syncope. They should also report clinical changes that could lead to hypokalaemia, such as gastroenteritis or the initiation of diuretic therapy. At each medical visit, risk factors should be revisited.
Apomorphine is associated with local subcutaneous effects. These can sometimes be reduced by the rotation of injection sites or possibly by the use of ultrasound (if available) in order to avoid areas of nodularity and induration (see Section 4.8 Adverse Effects (Undesirable Effects)).
Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine. Haematology tests should be undertaken at regular intervals as with levodopa, when given concomitantly with apomorphine.
Caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Neuropsychiatric problems co-exist in many patients with advanced Parkinson's disease. There is evidence that for some patients neuropsychiatric disturbances may be exacerbated by apomorphine. Special care should be exercised when apomorphine is used in these patients. Apomorphine has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with apomorphine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction of dosage or termination of therapy may be considered.
The use of apomorphine in conjunction with levodopa treatment may cause Coombs' positive haemolytic anaemia. An initial screen prior to commencement of treatment and at 6 monthly intervals is recommended. In the event of the development of a haemolytic anaemia, a haematological specialist should be consulted. The dose of apomorphine and/or levodopa should be reduced, with careful monitoring of the patient's motor state. It may be necessary to discontinue treatment with levodopa and/or apomorphine in the event that it is not possible to control the anaemia satisfactorily.
Apomorphine should be used with caution in patients with endocrine, renal, pulmonary or cardiovascular disease.
Periodic evaluation of hepatic, haemopoietic, renal and cardiovascular function is advised.
Patients with severe renal insufficiency may require the dosing interval for domperidone to be less frequent (see Section 4.2 Dose and Method of Administration, Pre-treatment).

Neuroleptic malignant syndrome.

Dopamine agonist withdrawal syndrome.

Impulse control disorders.

Use in debilitated patients.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients selected for treatment with apomorphine are almost certain to be taking concomitant medications for their Parkinson's disease. In the initial stages of apomorphine therapy the patient should be monitored for unusual side-effects or signs of potentiation of effect.
Drugs which interfere with central amine mechanisms such as tetrabenazine, metoclopramide, antipsychotic dopamine blocking agents (such as phenothiazines, thioxanthenes and butyrophenones), amphetamines and papaverine should be avoided. If their administration is considered essential, extreme care should be taken and the patient monitored for signs of potentiation, antagonism or other interactions and for any unusual adverse effects.
Neuroleptic medicinal products may have an antagonistic effect if used with apomorphine. There is a potential interaction between clozapine and apomorphine.
The possible side effects of apomorphine on the plasma concentrations of other medicinal products have not yet been studied. Therefore caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range.
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with 5HT₃ antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) is contraindicated (see Section 4.3 Contraindications).

Antihypertensive and cardiac active medicinal drugs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Apomorphine has varying degrees of impairment which influences the ability to drive and use machines.
Patients being treated with apomorphine and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities (e.g. operating machines) where impaired alertness may put themselves or others at risk of serious injury or death until such recurrent episodes and somnolence have resolved (also see Section 4.4 Special Warnings and Precautions for Use).

4.8 Adverse Effects (Undesirable Effects)

Very common (> 10%).

Common (1-10%).

Uncommon (0.1-1%).

Rare (0.01-0.1%).

Not known (can not be estimated from available data).

Reporting suspected adverse effects.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Symptoms.

Treatment.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

The peripheral pharmacokinetics of apomorphine have been studied following subcutaneous injection, subcutaneous infusion and intravenous infusion.

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfite.
Water for injections.
Hydrochloric acid may also be included in the formulation to adjust the pH. The pH of the injection is 3.0 to 4.0.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
For microbial reasons, once opened the contents of the pre-filled syringe should be used for infusion immediately. Any unused solution should be discarded.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light. (Keep the container in the outer carton).

6.5 Nature and Contents of Container

Clear glass (Type 1) pre-filled syringe with a chlorobutyl rubber stopper and tip.
Packs contain 5 x 10 mL (5 mg/ mL) pre-filled syringes.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements. After single use, adaptors and plastic syringes should also be discarded and disposed of in a "Sharps" bin.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes